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KMID : 0861120130170020169
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Korean Journal of Oriental Preventive Medicine
2013 Volume.17 No. 2 p.169 ~ p.178
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Saussurea Lappa Radix-induced cytotoxicity via ROS generation in A549 lung cancer cells
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Lee Young-Joon
Kang Su-Jin
Ku Sae-Kwang
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Abstract
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Objectives : Many cancers acquired resistance to chemotherapy, thus limiting its anticancer efficacy. It is known that Glutathione (GSH) is related to the development of drug resistance. The expression of GSH synthesizing glutamylcysteine ligase (GCL) was controlled by nuclear factor-E2-related factor (Nrf2). Previous studies showed that pharmacological depletion of GSH results in ROS increase, apoptotic response, and sensitization to oxidizing stimuli. In the current study, we examined Saussurea Lappa (SL) have the inhibitory effecton Nrf2 activity using human lung cancer A549 cells over expressing Nrf2.
Methods : Cellviability of A549 cells on SL treatment was determined by MTT assay.To detect the apoptosisin SL-treated A549 cells, sub-G1 population was measured by flow cytometry analysis (FACS). The level ROS was determined by FACS and fluorescence microscopy. To investigate whether SL have effect the suppression on Nrf2, we performed western blotting analysis. The GSH content was measured since GSH plays an important role in response to oxidative stress and was regulated by Nrf2.
Results : A549 cells treated with an SL extract showed as ubstantial decrease in cellviability, along with aconcomitant increase in apoptosis compared toun treated cells. Treatment of the SL extract led to increased Reactive oxygen species (ROS) production and a suppression of Nrf2. In addition, the antioxidant NAC attenuated SL-induced ROS generation, Nrf2 inhibition, and apoptosis. Taken to gether, these data show that the SL extract induced the production of ROS, and the inhibition of Nrf2, consequently resulting in A549 cell death.
Conclusions : These results suggest that SL might be an effective agent to enhance anticancer drug sensitivity via Nrf2 inhibition
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KEYWORD
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Saussurea Lappa Radix, Nrf2, ROS, GSH, A549
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